Adverse effects of creatine supplementation: fact or fiction?

The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects in healthy individuals. Nevertheless, idiosyncratic effects may occur when large amounts of an exogenous substance containing an amino group are consumed, with the consequent increased load on the liver and kidneys. Regular monitoring is compulsory to avoid any abnormal reactions during oral creatine supplementation.

Effect of exogenous creatine supplementation on muscle PCr metabolism.

31P NMR was used to assess the influence of two weeks creatine supplementation (21g x d(-1)) on resting muscle PCr concentration, on the rate of PCr repletion (R(depl)), and on the half-time of PCr repletion (t 1/2). Body mass (BM) and volume of body water compartments were also estimated by impedance spectroscopy. Fourteen healthy male subjects (20.8+/-1.9 y) participated in this double-blind study. PCr was measured using a surface coil placed under the calf muscle, at rest and during two exercise bout the duration of which was 1 min. They were interspaced by a recovery of 10 min. The exercises comprised of 50 plantar flexions-extensions against weights corresponding to 40% and 70% of maximal voluntary contraction (MVC), respectively. Creatine supplementation increased resting muscle PCr content by approximately 20% (P= 0.002). R(depl) was also increased by approximately 15% (P< 0.001) and approximately 10% (P = 0.026) during 40% and 70% MVC exercises, respectively. No change was observed in R(repl) and t1/2. BM and body water compartments were not influenced. These results indicate that during a standardized exercise more ATP is synthesized by the CK reaction when the pre-exercise level in PCr is higher, giving some support to the positive effects recorded on muscle performance.

Long-term oral creatine supplementation does not impair renal function in healthy athletes.

PURPOSE: Oral creatine supplementation is widely used in sportsmen and women. Side effects have been postulated, but no thorough investigations have been conducted to support these assertions. It is important to know whether long-term oral creatine supplementation has any detrimental effects on kidney function in healthy population. METHODS: Creatinine, urea, and plasma albumin clearances have been determined in oral creatine consumers (10 months to 5 yr) and in a control group. RESULTS: There were no statistical differences between the control group and the creatine consumer group for plasma contents and urine excretion rates for creatinine, urea, and albumin. Clearance of these compounds did not differ between the two groups. Thus, glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability were normal in both groups. CONCLUSIONS: Neither short-term, medium-term, nor long-term oral creatine supplements induce detrimental effects on the kidney of healthy individuals.

Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation.

Strenuous exercise may be associated with immune suppression. However, the underlying mechanism is not known. A decrease in the plasma level of glutamine, which is utilised at a high rate by cells of the immune system, and an increase in the plasma level of some cytokines may impair immune functions such as lymphocyte proliferation after prolonged, exhaustive exercise. In two separate studies of the Brussels marathon, using similar protocols, the time course of the changes in the plasma concentrations of some amino acids (glutamine, glutamate, alanine, tryptophan and branched chain amino acids), acute phase proteins and cytokines (interleukins IL-1 alpha, IL-2, IL-6, tumour necrosis factor type a) was measured in male athletes. The numbers of circulating leucocytes and lymphocytes were also measured. Amino acid and cytokine concentrations have not previously been measured concomitantly in marathon runners; the measurement of some of these parameters the morning after the marathon (16 h) is novel. Another novel feature is the provision of glutamine versus placebo to marathon runners participating in the second study. In both studies the plasma concentrations of glutamine, alanine and branched chain amino acids were decreased immediately after and 1 h after the marathon. Plasma concentrations of all amino acids returned to pre-exercise levels by 16 h after exercise. The plasma concentration of the complement anaphylotoxin C5a increased to abnormal levels after the marathon, presumably due to tissue damage activating the complement system. There was also an increase in plasma C-reactive protein 16 h after the marathon. The plasma levels of IL-1 alpha were unaffected by the exercise, while that of IL-2 was increased 16 h after exercise. Plasma IL-6 was increased markedly (approximately 45-fold) immediately after and at 1 h after exercise. Neopterine, a macrophage activation marker, was significantly increased post-exercise. There was a marked leucocytosis immediately after the marathon, which returned to normal 16 h later. At the same time there was a decrease in the number of T-lymphocytes, which was further reduced within 1 h to below pre-exercise levels. Glutamine supplementation, as administered in the second study, did not appear to have an effect upon lymphocyte distribution.